Coloproctology

Correction to: Long-term results of stapled hemorrhoidectomy Unfortunately, there is a spelling mistake in the 2nd sentence of the 2nd paragraph. The complete correct sentence is given below.

Cost-analysis and quality of life after laparoscopic and robotic ventral mesh rectopexy for posterior compartment prolapse: a randomized trial Abstract Background The aim of this study was to assess, whether robotic-assistance in ventral mesh rectopexy adds benefit to laparoscopy in terms of health-related quality of life (HRQoL), cost-effectiveness and anatomical and functional outcome. Methods A prospective randomized study was conducted on patients who underwent robot-assisted ventral mesh rectopexy (RVMR) or laparoscopic ventral mesh rectopexy (LVMR) for internal or external rectal prolapse at Oulu University Hospital, Finland, recruited in February–May 2012. The primary outcomes were health care costs from the hospital perspective and HRQoL measured by the 15D-instrument. Secondary outcomes included anatomical outcome assessed by pelvic organ prolapse quantification method and functional outcome by symptom questionnaires at 24 months follow-up. Results There were 30 females (mean age 62.5 years, SD 11.2), 16 in the RVMR group and 14 in the LVMR group. The surgery-related costs of the RVMR were 1.5 times higher than the cost of the LVMR. At 3 months the changes in HRQoL were 'much better' (RVMR) and 'slightly better' (LVMR) but declined in both groups at 2 years (RVMR vs. LVMR, p > 0.05). The cost-effectiveness was poor at 2 years for both techniques, but if the outcomes were assumed to last for 5 years, it improved significantly. The incremental cost-effectiveness ratio for the RVMR compared to LVMR was €39,982/quality-adjusted life years (QALYs) at 2 years and improved to €16,707/QALYs at 5 years. Posterior wall anatomy was restored similarly in both groups. The subjective satisfaction rate was 87% in the RVMR group and 69% in the LVMR group (p = 0.83). Conclusions Although more expensive than LVMR in the short term, RVMR is cost-effective in long-term. The minimally invasive VMR improves pelvic floor function, sexual function and restores posterior compartment anatomy. The effect on HRQoL is minor, with no differences between techniques.

Assessment of the Versius surgical robotic system for dual-field synchronous transanal total mesorectal excision (taTME) in a preclinical model: will tomorrow's surgical robots promise newfound options? Abstract Background The aim of this study was to evaluate the feasibility of the Versius surgical robotic system for transanal total mesorectal excision (taTME) in a preclinical setting. Methods Dry laboratory and cadaveric sessions were first conducted for three experienced colorectal surgeons in order to gain familiarity with the modular surgical system and the robotic workstation. After introduction, the system was configured to allow for synchronous, totally robotic taTME in a cadaver. Results Using the modular robotic system, one surgeon performed the abdominal portion of the operation, including colonic mobilization and vascular pedicle ligation while simultaneously a second surgeon performed the transanal portion of the operation to the point of rendezvous at the peritoneal reflection, where the operation was completed cooperatively. The operation was successfully completed in 195 min demonstrating preclinical feasibility of this unique approach with an emerging robotic system. Conclusions This is the first preclinical assessment of the Versius surgical robotic system for taTME. The ability to work simultaneously carries the theoretical advantage of reducing surgical time and thereby reducing overall operative costs. It may also allow surgeons to maintain focus on critical parts of the operation by halving the fatigue associated with long, complex cases such as taTME.

Radiofrequency ablation for haemorrhoidal disease: description of technique

An imaginary cuboid: chest, abdomen, vertebral column and perineum, different parts of the same whole in the harmonic functioning of the pelvic floor

The clinical efficacy of stem cell therapy for complex perianal fistulas: a meta-analysis Abstract Background Treatment of complex anal fistulas remains difficult. However, treatment with stem cells has had an encouraging success rate when applied to complex perianal fistulas. We systematically reviewed the current evidence through meta-analysis. Methods We performed an electronic literature search on PubMed, Embase, and the Cochrane Library and identified studies (published between January 1946 and August 2017) that used stem cells to treat patients with complex perianal fistula. Each paper was evaluated for treatment success rate, target patients, types of stem cells used, number of cells used, and criteria for complete healing. Potential publication bias was assessed via visual inspection of a funnel plot and Orwin's fail-safe N. Out of 171 papers, 16 were included in the meta-analysis. Results The overall healing rate of stem cell injection therapy for patients with complex perianal fistulas was 62.8% (95% CI 53.5–71.2, I2 = 54.05%), whereas those for patients with Crohn's perianal fistulas alone and complex anal fistulas not associated with Crohn's disease were 64.1% and 61.5% (p = 0.840), respectively. Healing rates for autologous and allogenic stem cell treatment were 69.4% and 50.7% (p = 0.020), respectively. Four comparative studies out of 16 studies were analyzed separately. Stem cell therapy increased the healing rate compared to the control groups (OR 0.379, 95% CI 0.152–0.947). Conclusions Stem cell therapy is a good treatment option for complex perianal fistulas, which cannot be healed by conventional operative procedures. However, further research for additional supportive evidence, such as a large-scale randomized controlled trial, is required.

Disparities in colostomy reversal after Hartmann's procedure for diverticulitis Abstract Background Hartmann's procedure for diverticulitis is a common procedure, with highly variable rates and timing of colostomy reversal. The aim of this study was to evaluate the impact of race and insurance coverage on reversal within 2 years of Hartmann's procedure for diverticulitis. Methods The Healthcare Cost and Utilization Project (HCUP) State Inpatient Database of five states (2007–2010) was queried for patients who had Hartmann's procedure in the setting of diverticulitis. Patients were grouped by race and insurance status, and multivariable adjustment was performed to evaluate rate and timing of colostomy takedown at 2 years. Results Among 11,019 patients who had Hartmann's procedure for diverticulitis, 6900 (69%) patients had colostomy reversal by 2 years, with a median time to reversal of 19 weeks. Compared to white patients with private insurance, combinations of black race and non-private insurance significantly reduced likelihood of colostomy reversal at 2 years across all combinations. Black patients without insurance had the lowest likelihood of reversal at 2 years (OR 0.27, 95% CI 0.14–0.51, p < 0.001). For patients who had colostomy reversal within 2 years, black patients without insurance had a significant delay in time to reversal (11 weeks, 95% CI 6–16, p < 0.001) compared to white patients with private insurance, and delays persisted across all other groups. Conclusions Black patients and those without private insurance experienced significantly lower rates of, and delayed time to, colostomy reversal compared to white patients with private insurance. These disparities must be considered for allocation of resources in marginalized communities.

Ultrasound-guided identification of superior mesenteric vein in robotic complete mesocolic excision for right colon cancer

Totally intracorporeal robotic en bloc resection for deep infiltrating endometriosis of the rectovaginal wall with natural orifice specimen extraction

Transanal minimally invasive surgery (TAMIS) for anterior rectal GIST

Pharmacology and Pharmacotherapeutics

Structural genomics in drug discovery: An overview Karri Sowjanya, Chandrashekaran Girish Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):1-6 Structural genomics, technology and methodology driven field has emerged in the past 20–25 years and mainly aims at coming up with as many three-dimensional structures of proteins as possible by combining experimental (X-ray crystallography and nuclear magnetic resonance) and comparative modeling methods at a minimal cost in comparison to the traditional approaches. Structure aided drug discovery which is used since long mainly focuses on a single target protein whereas structural genomics targets and investigates multiple proteins simultaneously, thus cutting down time and cost. These activities are done at specialized structural genomic centers available worldwide that help to interpret the biology of humans and pathogenic organisms in a better way leading to an increased productivity and saving time. Virtual screening methods like docking have also brought a great impact to quicken the drug discovery process. In diseases of public health concern (like tuberculosis), structural genomics helped greatly by giving important insights toward a better comprehension of the pathways associated in its pathogenesis and in guiding drug discovery. Several newer targets such as Scaff10-8, MS2734 (6), and GSK-J4 were developed showcasing their beneficial effects in a wide variety of disorders including diabetes insipidus, Parkinson's disease, and autoimmune diseases, respectively. Furthermore, these programs guide to understand the root cause and the mechanism associated with various human diseases and their pathogens. This review tries to look into the high throughput methods of structure determination, the newer targets developed in the past few years and the benefits offered that can pave a way for faster and efficient drug discovery.

Genotype and allele frequency of p450 oxidoreductase *28 gene polymorphism in South Indian population R Mirunalini, G Pavithra, D Benet Bosco Dhas, C Adithan Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):7-10 Objective: To establish the normative frequency of POR *28 genetic variant in South Indian population. Methods: This study is a genetic epidemiological study conducted on healthy volunteers belonging to south India. A total of 108 healthy volunteers who satisfied the eligibility criteria were included in the study. The DNA isolation was done using the QIAGEN Blood DNA isolation kit (Qiagen). The genotyping for POR *28 polymorphism was done using TaqMan genotyping master mix kits (Applied Biosystems) in real-time polymerase chain reaction platform. The data were analyzed using Fisher's exact test. P < 0.05 was considered statistically significant. Hardy–Weinberg principle was tested using the Chi-square test. Results: The genotyping of the POR *28 showed that the wild-type (homozygous) in the south Indian population was 41.7% and heterozygous and mutant type as 47.2% and 11.1%, respectively. The allele frequency showed that the minor allele frequency (MAF) was 34.7% in the south Indian population. This distribution of allele frequency was found to be significantly different from that of African–Americans 0.191 (95% confidence interval 0.157, 0.231). It was not statistically significant when compared to Caucasians 0.264 (0.228, 0.304); Chinese 0.367 (0.319, 0.419); Mexicans 0.310 (0.265, 0.360); and Japanese 0.40 (0.339, 0.464). Conclusion: The frequency distribution of POR *28 genetic variant was established in the south Indian population. The MAF was found to be 34.7% which was significantly different from other major ethnic groups.

Comparison of safety and efficacy of dexmedetomidine versus propofol sedation for elective awake fiber-optic intubation Samarjit Dey, Tridip Jyoti Borah, Jaideep Sonowal, Debasis Pradhan, Md. Yunus, Priyanka Dev Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):11-15 Objective: To evaluate the safety and efficacy of dexmedetomidine versus propofol as a sedative modality for awake fiber-optic intubation (AFOI) in elective patients with anticipated difficult intubation. Materials and Methods: This randomized prospective study was conducted on 90 patients (Group D and Group P; n = 45) who had undergone AFOI for anticipated difficult airway. Group D received intravenous (IV) dexmedetomidine and Group P patients received IV propofol, until they were adequately sedated. Sedation was measured by Bispectral index© and Ramsay Sedation Scale. Airway blocks were given to all patients undergoing awake fiber-optic intubation. Intubation comfort scores, airway obstruction scores, and hemodynamics were recorded in all patients. Results: Sedation level was comparable in both the groups. Intubation time was less in Group D than Group P (119.06 ± 16.51 s vs. 126.67 ± 18.19 s; P < 0.05). The intubation score for both cough and vocal cord opening was better in the dexmedetomidine group than the propofol group (P = 0.6). There were significant incidences of airway obstruction and hypoxia in Group P compared to Group D (P < 0.05). Significant fall in mean arterial pressure (MAP) was seen in Group P during drug infusion which continued till fiber-optic bronchoscopy (P < 0.05). MAP changes during intubation were similar during intubation in both the groups (P = 0.18). Conclusion: Dexmedetomidine is a better alternative for achieving optimal sedation during AFOI.

Antidepressants modulate behavioral, biochemical, and histological alterations induced by chronic aluminum chloride administration in wistar rats Arshad Basha Shaik, Smita Shenoy, V Anupama, K G Mohandas Rao, Arul Amuthan Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):16-21 Objective: To assess the effect of duloxetine and escitalopram on aluminum chloride (AlCl3)-induced memory impairment in rats. Materials and Methods: Thirty rats were used. Group-I (control) and Group-II (toxic control) received 2% gum acacia, 10 mL/kg and AlCl3, 175 mg/kg, respectively. Group-III (standard), Group-IV, and Group-V (test drug groups) received rivastigmine (1 mg/kg), duloxetine (10 mg/kg), and escitalopram (10 mg/kg), respectively, along with AlCl3, 175 mg/kg. All drugs and AlCl3 were administered orally daily for 2 months. The effect on cognition was assessed by Morris water maze (MWM). Brain acetylcholinesterase levels, oxidative stress parameters, and histology of the hippocampus were also evaluated. Results: Rats treated with only AlCl3 showed significant (P < 0.001) increase in latency during acquisition trials of day-3 and day-4 and decrease in percentage of both time spent and distance traveled in target zone during probe trial in MWM. Malondialdehyde was increased and glutathione decreased in the brain. Histopathology of the hippocampus showed unhealthy cellular architecture with a large number of degenerated cells. All these changes were significantly reversed in rivastigmine and test drug groups. Chronic administration of AlCl3 resulted in lowering of brain cholinesterase levels (P < 0.001) versus control. Cholinesterase levels were further significantly (P < 0.05) lowered in rats who received AlCl3 along with either rivastigmine or escitalopram. Conclusion: Escitalopram and duloxetine exerted a protective effect against AlCl3-induced memory impairment in rats.

Pharmacokinetic modeling of propofol in Indian children B Naveen Naik, Preethy J Mathew, Smita Pattanaik, Venkateswari Muthukrishnan, Goverdhan Dutt Puri Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):22-32 Objective: To analyse the PK (pharmacokinetics) of propofol after single bolus dose in children undergoing elective general surgery and to establish a PK model of propofol after single bolus dose in children undergoing elective general surgery and to establish a PK model of propofol. Materials and Methods: Twelve healthy Indian children aged 5–12 years who underwent elective general surgery under general anesthesia received propofol at an intravenous bolus dose of 2.5 mg/kg. The plasma propofol concentration over the next 12 h was estimated using high-performance liquid chromatography. A total of 144 samples were analyzed, and PK parameters were evaluated using nonlinear mixed-effects modeling. Results were validated using bootstrap analysis, and visual predictive check was done to evaluate the final model. Results: Propofol PK in Indian children was characterized by a three-compartment model similar to adults. The model derived estimates of PK parameters are as follows: volume of the central compartment (V1) = 598.73 ml/kg, volume of the second compartment (V2) = 821.12 ml/kg, volume of the third compartment (V3) = 1097 ml/kg, systemic clearance (CL1) = 22.1 ml/kg/min, and intercompartmental clearances CL2 and CL3 which were 42.5 ml/kg/min and 10.4 ml/kg/min, respectively. Conclusion: The final PK model imparted a robust characterization of propofol PK. Inclusion of body weight as a covariate to the model exhibited a significant impact on propofol PK. The execution of this patient derived PK model should support future population PK studies that include diverse population with sparse sampling to support the dosing of propofol in Indian children undergoing surgery under total intravenous anesthesia.

Targeted spontaneous reporting on drug safety alerts issued by pharmacovigilance programme of India: A new origin of pharmacovigilance in India Prasad Thota, Shabir Sidhu, Bikash Medhi, Phulen Sarma, Ajay Prakash, Kalaiselvan Vivekanandan, Anusha Thota Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):33-34

Persistent cryptococcal meningitis treated with antiretroviral therapy and alternative antifungals Katie E Barber, Svenja Albrecht, Kayla R Stover Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):35-37 Because of the relative lack of information surrounding persistent cryptococcal meningitis, treatment presents a clinical dilemma. We report two patients who developed persistent cryptococcal meningitis that was nonresponsive to induction therapy over the course of several weeks. In the first patient, induction therapy with amphotericin and flucytosine was extended. Because of persistently high opening pressures (OPs) and cryptococcal antigen titers at 10 weeks, antiretroviral therapy with the combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was initiated, and the patient's OP and cryptococcal titers normalized within a week. This patient was well at his 2-week visit but was lost to follow-up after that. In the second patient, induction therapy with amphotericin and flucytosine was continued for 6 weeks due to persistently elevated OPs and cryptococcal antigen titers. At that time, high-dose fluconazole was added. This patient steadily improved and was discharged on fluconazole consolidation therapy. After hospital discharge, this patient was lost to follow-up. Published risk factors for persistent infection that these patients shared were positive human immunodeficiency virus status, elevated cryptococcal antigen titers, and persistently high OP. After initiation of unique, nonstandard therapy of antiretrovirals and high-dose fluconazole, both patients improved. Other potential treatment options for persistent cryptococcal meningitis include voriconazole, posaconazole, interleukin 2, acetazolamide, and the placement of cerebrospinal fluid shunts, but these were not selected because of a variety of relative contraindications or limitations of these agents. With limited data to favor one agent over another, it is important to evaluate case-by-case for treatment decisions.

Valproic acid induced pancreatitis in an Arab Male Ethar Abdelmageed Imam, Abdulrhman Idrees, Mohamed Izham Mohamed Ibrahim, Subish Palaian Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):38-41 Valproate, a commonly used antiepileptic, is known to cause pancreatitis, which may present days to years after initiation of therapy. A 20-year-old Arab male patient with electroencephalogram (EEG) confirmed epileptiform activity over the left posterior head region was initiated with tablet carbamazepine 400 mg twice daily in the year 2015 and based on subsequent EEG findings (suggestive of more of generalized myoclonic seizure) carbamazepine was withdrawn gradually and started with sodium valproate 500 mg twice daily and levetiracetam 1 g twice daily. During treatment, the patient had status epileptics, treated with diazepam and lamotrigine 50 mg was added. Laboratory data indicated low valproate level, 47 μg/mL (normal range: 50–125 μg/mL) resulting in two episodes of myoclonic jerks necessitating lamotrigine dose escalation (100 mg twice daily). A month later, the patient developed nystagmus and tremors, and lamotrigine dose was deescalated to 75 mg twice daily. Patient was brought to the emergency with severe abdominal pain and vomiting since the day before and valproate level was 179 μg/mL (>150 μg/mL μg/mL is considered toxic), a diagnosis of acute pancreatitis due to valproate was made and the patient was treated in the intensive care unit. The causality assessment of the adverse drug reaction was “probable” (Naranjo score 8), and severity was “Severe” (Level 5; Modified Hartwig and Siegel scale), and the adverse reaction was “Not preventable” (Modified Schumock and Thornton scale). This report suggests the need for constant clinical monitoring and the need for therapeutic drug monitoring for patients undergoing valproate therapy.

Subconjunctival bevacizumab for recurrent conjunctival pyogenic granuloma Nirupama Kasturi, Tharini Senthamizh, Hanuman Srinivas Bheemanathi, K Ramesh Babu Journal of Pharmacology and Pharmacotherapeutics 2019 10(1):42-44 A 45-year-old male presented with a pyogenic granuloma of the bulbar conjunctiva of the left eye following a stick injury. It was a benign friable, hyperplastic, vascular lesion comprised of inflammatory cells and lobular capillary proliferation. The differential diagnosis includes squamous papillomas, hemangiomas, suture granulomas, and ocular surface tumors, such as squamous cell carcinoma and amelanotic melanoma. Conventional treatment includes topical corticosteroids and surgical excision. Treatment of recurrent lesions with cryotherapy, electrocautery, topical antimetabolites, and plaque irradiation has been described. We present a case of recurrent pyogenic granuloma successfully treated with two subconjunctival bevacizumab injections. The patient developed three recurrences after excision at a peripheral hospital after which he was successfully treated with excision and adjuvant subconjunctival bevacizumab 2.5 mg/0.1 ml injection. This case highlights the novel use of bevacizumab for recurrent pyogenic granuloma.

Conservation Genetics

A carnivores' oasis? An isolated fisher ( Pekania pennanti ) population provides insight on persistence of a metapopulation Abstract Landscape level species assessments are rarely available to inform conservation planning. Recent advances in multi-taxa survey techniques, however, have made them more obtainable by improving efficiency of collecting species occurrence data and genetic samples. Here, we used a multi-taxa survey technique to provide a landscape level portrait of fisher (Pekania pennanti) population status in a portion of the northern Rockies where the species' history has been heavily influenced by humans. From 2010 to 2014 we deployed 497 winter forest carnivore bait stations across a 23,000 km2 study area centered on northern Idaho, United States. The stations collected remote camera images and hair samples for DNA analysis. We used 12 microsatellite loci to identify 58 individual fisher in the study area. We identified two fisher populations for which we estimated effective population size (Ne) and genetic neighborhood size (NS). We calculated local genetic diversity measures [observed (Ho) and expected (He) heterozygosity, allelic richness (Ar), fixation index (FST), and number of migrants per generation (Nm)] and mapped continuous gradients of genetic diversity [Ar and inbreeding coefficient (FIS)] across the study area. We identified a fisher population in the West Cabinet Mountains [Ne of 26 (15.3–55.5), NS of 50–60] which is effectively isolated from the small population we detected in the Saint Joe/Coeur d'Alene Mountains [Ne of 6.5 (2.7–15), NS of 10–25]. We determined fisher have been effectively extirpated from the Selkirk and Purcell mountains and the lack of genetic connectivity between the two small remaining populations casts doubt on long term viability. Our study suggests northern Rockies fisher populations are vulnerable to landscape barriers and successful recovery will depend on future management and augmentation. We recommend these factors be considered when determining how, and if, species recovery should proceed.

Lack of spatial and temporal genetic structure of Japanese eel ( Anguilla japonica ) populations Abstract Japanese eel (Anguilla japonica) is an important food source in East Asia whose population has dramatically declined since the 1970s. Despite past analysis with DNA sequencing, microsatellite and isozyme methods, management decisions remain hampered by contradictory findings. For example, it remains unresolved whether Japanese eels are a single panmictic population or whether they harbor significant substructure. Accurate assessment of population genetic substructure, both spatial and temporal, is essential for determining the relevant number of distinct management units appropriate for this species. In the present study, we assayed genetic variation genome-wide using Restriction Site Associated DNA Sequencing (RAD-seq) technology to analyze the population genetic structure of Japanese eels. For analysis of temporal isolation, five "cohort" samples were collected yearly from 2005 to 2009 in the Yangtze River Estuary. For analysis of spatial structure, five "arrival wave" samples were collected in China in 2009, and two arrival wave samples were collected in Japan in 2001. In each cohort of each arrival wave, five individuals were collected for a total of 55 eels sampled. In total, 214,210 loci were identified from these individuals, 106,652 of which satisfied quality checks and were retained for further analysis. There was relatively little population differentiation between arrival waves and cohorts collected either at different locations during the same year (Fst = 0.077) or at the same location collected over subsequent years (Fst = 0.082), and locations displayed no consistent isolation-by-distance.

Assessing the contribution of aquaculture and restoration to wild oyster populations in a Rhode Island coastal lagoon Abstract The decline of the eastern oyster (Crassostrea virginica) has prompted various restoration and aquaculture efforts. Recent field surveys in Rhode Island suggest that wild populations are increasing, yet the factors contributing to expansion are unknown. We used a population genetic approach to characterize genetic differences between wild and cultured oyster populations and explore the extent of connectivity and admixture between groups. Individual oysters from four wild, three farmed, and two restored populations were collected within or just outside Ninigret Pond, a coastal lagoon highly influenced by human activity, and genotyped at 13 microsatellite loci. Results from the multi-locus genotype data showed that wild populations were more genetically diverse than the cultured populations. We also observed significant genetic differentiation between paired wild and cultured populations but not between pairs of wild populations. A cluster analysis detected substantial admixture between wild and cultured groups. As oyster aquaculture and restoration activities are forecasted to increase in the future, this study highlights the potential degree of genetic introgression between remnant wild populations and less diverse, hatchery-reared stocks. Those tasked with preserving our living natural resources should carefully consider how the juxtaposition of aquaculture, restored, and wild populations at small spatial scales will impact the genetic composition and evolutionary trajectories of species in decline for generations to come.

Distribution, fine-scale subdivision, and population size of San Joaquin kit foxes in the Ciervo-Panoche Natural Area, California Abstract The endangered San Joaquin kit fox (SJKF; Vulpes macrotis mutica) is strongly linked ecologically to xeric areas with high abundance of kangaroo rats. Endemic to the San Joaquin Desert of central California, the elusive nature of SJKF, coupled with steady habitat loss and lack of comprehensive surveys, has precluded efforts to quantify the species' population size and distribution, especially in the central and northern parts of its range. Because the Ciervo-Panoche Natural Area contains the largest area of high-quality habitat in this central/northern region, we conducted systematic transect surveys for SJKF scats with professionally trained dog-handler teams throughout the area during 2009–2011. We collected almost 600 scats over 473 km of transects, documenting the freshness and location of each scat. Using molecular methods, we identified 93 SJKF individuals (56 males and 37 females) from 332 samples. Half of the individuals carried a mtDNA haplotype with a 16 bp deletion that had not been previously detected in other areas surveyed. Four individuals were recaptured in 2010 and five in 2011, including one female that was captured every year. We documented a unique mtDNA haplotype and more individuals across a wider area of the Ciervo-Panoche Natural Area than expected. Population analyses revealed two distinct subpopulations, with low connectivity between foxes in the Panoche Valley that are separated by hills with unsuitable habitat from those on the adjacent valley floor next to a major Interstate highway (I-5). While individuals detected within 6 km of each other were closely related, overall relatedness within each subpopulation approached zero. Genetic population models indicated a conservative population estimate of 90 kit foxes in total, with 60–90 individuals in the Panoche Valley and 17–27 individuals in the I-5 area. These results will help to inform management of the SJKF and identify areas that may be important to maintaining connectivity between populations.

Genetic diversity and population demography of Geranium soboliferum var. kiusianum : a glacial relict plant in the wetlands of Japan Abstract Geranium soboliferum var. kiusianum and var. hakusanense (Geraniaceae) are believed to be relict plants that migrated southward from the Eurasian continent to the Japanese archipelago during the last glacial period. G. soboliferum var. kiusianum individuals and populations, which occur in wetlands in the Aso-Kuju region of Kyushu Island, are declining as a result of the deteriorating quality of the microhabitat, a process that is associated with the decrease in semi-natural grasslands. Using 10 polymorphic microsatellite markers, we evaluated the genetic diversity and population structure of the G. soboliferum complex, with the aim of understanding the species' genetic characteristics to facilitate efficient conservation. Genetic demographic analysis suggested that Japanese G. soboliferum populations branched off from the Eurasian continental G. soboliferum var. soboliferum during the last glacial period and that, thereafter, the Japanese populations of the plant diverged into two lineages at the beginning of the Holocene epoch. The genetic diversity of G. soboliferum var. kiusianumwas significantly lower than that of var. hakusanense, which is more widely distributed in central Honshu Island (mean Ar = 3.288 vs. 3.830 and He = 0.366 vs. 0.546). Genetic differentiation among populations was significantly higher (mean FST = 0.368 vs. 0.184) in var. kiusianum populations and, notably, exhibited non-significant patterns of isolation by distance, indicating that the populations underwent strong genetic drift independent of adjacent populations. Our findings suggested that the population's isolation, and its associated habitat specialization and limited inter-population gene flow, would have accelerated genetic differentiation in var. kiusianum. Overall, G. soboliferum var. kiusianum, which is genetically unique to wetland habitats in the Aso-Kuju region, merits conservation, and appropriate human intervention and management are critical to maintaining its remaining habitats in semi-natural grasslands.

Conservation genetic analysis of a Central-European range-margin population of the yellow-bellied toad ( Bombina v. variegata ) Abstract The aim of this study was to investigate the genetic structure and diversity of populations of the yellow-bellied toad in Lower Saxony, Germany. These populations provide a good example of a fragmented distribution of amphibian pioneer species on the outer rim of their occurrence. In total, 150 individuals from 11 sites were genotyped using ten highly polymorphic microsatellites. The genetic diversity, as measured by allelic richness and heterozygosity, was lower than that of other European amphibian populations; the individuals could be assigned to five genetic clusters. The average genetic differentiation between populations was very high (mean FST = 0.27) and no migration was detected between the two major populations, which were about 50 km apart. Nonetheless, natural migration as well as translocations between some subpopulations could be detected. In one population, which was introduced in the 1970s, we were able to verify the potential source population of the introduced toads. The results are discussed in light of conservation management strategies applied to this highly endangered species.

Genetic diversity and population structure of Kichulchoia multifasciata in South Korea Abstract Kichulchoia multifasciata, a small-sized loach (Family Cobitidae) inhabiting only the Nakdong River on the Korean Peninsula, is generally found around well-oxygenated minor tributaries. Despite the scarcity, this species is not yet a legally protected species in South Korea, and the spatial pattern of genetic diversity, which is essential to create management strategies, has never been studied. In this study, three mitochondrial loci and ten microsatellites were used to analyze the genetic diversity and the structure among eight K. multifasciata populations collected from different tributaries. K. multifasciata populations showed a high level of mitochondrial variability, with above 0.9 of average haplotype diversity in all three loci analyzed. A substantial microsatellite polymorphism was also found. Weak genetic structuring among populations and isolation by distance were clearly revealed in both mitochondrial and microsatellite data, indicating the high levels of gene flow among the tributaries. However, a few of the populations exhibited a genetic signature that they have experienced the historical size decline. Our data suggest that unequal gene flow might be one of the causes; nevertheless, the possibility of effective population size reduction by other factors could not be completely excluded. Our genetic evidence can be the critical information needed to protect the populations from the genetic erosion in the Nakdong River that has been destroyed and fragmented with increasing anthropogenic interferences.

Combining molecular and incomplete observational data to inform management of southern white rhinoceros ( Ceratotherium simum simum ) Abstract Conservation efforts have preserved the southern white rhinoceros (SWR) in protected areas and have resulted in substantial overall growth in population size, but in small, fragmented populations in which inbreeding is an important risk. However, field observation of breeding often lacks sufficient accuracy to inform translocation strategies that are intended to increase genetic variation. The purpose of this study was to integrate microsatellite genotypes with an incomplete, field-observed pedigree to make inferences about mean kinship and basic demographic data that could be used to inform translocation programmes for SWR in a confined population in Botswana. Using this approach, we identified parents for 29 out of 45 offspring born in the reserve between 1993 and 2013 and detected eight non-breeding bulls with high mean kinship as candidates for translocation. The method also allowed inferences about demographic parameters that could influence the effectiveness of intervention strategies, such as age and timing of reproduction, and natal sex ratios. Importantly, the reproductive dominance of the bulls was not as skewed as expected after the original dominant bull was removed from the population, suggesting that closed populations can maintain multiple, simultaneously breeding males. The genetic data also confirmed that the accuracy of field-based parentage assignment was increased after implementation of an ear-notching programme. This study demonstrates the value of combining genetic information with ongoing surveillance to inform management of threatened populations, and of using mean kinship to inform metapopulation management by identifying candidates for translocation.

Population genetics, speciation, and hybridization in Dicerandra (Lamiaceae), a North American Coastal Plain endemic, and implications for conservation Abstract Understanding patterns of speciation and subsequent gene flow can clarify the evolutionary origins and history of species endemic to a specific geographic region and reveal genetic patterns important for conservation and management of rare species. We chose Dicerandra from the North American Coastal Plain biodiversity hotspot as a model to explore these concepts because of its endemism and the threatened status of most of its species. Using microsatellite-based population-level analyses of 32 populations from four of the annual species (D. linearifolia var. linearifolia, D. linearifolia var. robustior, D. fumella, D. odoratissima, and D. radfordiana), we addressed questions of genetic diversity, population structure, and hybridization. Strong support was found for the species-level recognition of the recently described D. fumella from the Florida panhandle. Dicerandra linearifolia var. linearifolia showed some regional cohesion of populations, but there was no consistent geographic pattern to the clustering of populations. Dicerandra radfordiana showed consistent clustering with proximate populations of D. odoratissima. Given that D. radfordiana is found at the southeastern extreme of the range of D. odoratissima, these populations may represent the early stages of speciation by isolation. While there are morphological and bioclimatic niche distinctions between D. odoratissima and D. radfordiana, there is no molecular support for a distinct D. radfordiana. Overall, there is modest genetic diversity found at the population level for all Dicerandra annuals. Microsatellite data support previously proposed hypotheses of hybridization between D. linearifolia var. linearifolia and D. odoratissima, but do not support such hypotheses for D. fumella and D. linearifolia var. robustior.

Rangewide tidewater goby occupancy survey using environmental DNA Abstract Rangewide monitoring of fish species is critical for determining status and trends in distribution; however, implementations of large-scale distribution surveys have generally been constrained by time and cost. This study used environmental DNA (eDNA) to monitor the presence or absence of two endangered tidewater goby species, the northern tidewater goby (Eucyclogobius newberryi) and the southern tidewater goby (Eucyclogobius kristinae), across their combined geographic range that encompasses the entire California coast (1350 km). A total of 197 estuary sites were surveyed in coastal California from Del Norte to San Diego counties between May and September 2016. Among the 197 sites, a total of 430 water samples were collected (one to six per site), filtered, and tested for the presence/absence of northern and southern tidewater goby, using species-specific quantitative PCR assays. Northern tidewater goby were detected at 81 out of 175 sites and southern tidewater goby were detected at 4 out of 22 sites, resulting in a combined naïve occupancy of 0.43. In contrast, application of a multi-scale occupancy model that accounted for imperfect detection estimated site occupancy at 0.55 (95% CRI 0.46–0.64), indicating that tidewater goby were present but not detected at 23 additional sites. This study illustrates that eDNA methods represent a reliable and efficient tool for aquatic species monitoring, but highlight the importance of accounting for imperfect detection by use of occupancy models in eDNA surveys. The tidewater goby eDNA distributional snapshot represents a baseline for evaluation of future trends in site occupancy that will inform conservation and management of this endangered species.

Gastroenterology

The missing "C": Crohn's, colitis and coping Turki AlAmeel, Mahmoud Mosli Saudi Journal of Gastroenterology 2019 25(3):143-144

The regulatory roles of long noncoding RNAs in the biological behavior of pancreatic cancer Ying Li, Xiaojuan Yang, Xiaoning Kang, Shanglong Liu Saudi Journal of Gastroenterology 2019 25(3):145-151 Long noncoding RNAs (lncRNAs) are a new class of regulators. LncRNAs are defined as endogenous transcribed RNA molecules with transcript length of >200 nt. Accumulating evidence has shown that lncRNAs are involved in many physiological processes such as cell cycle regulation, cell apoptosis and survival, cancer migration and metabolism. However, the biological and molecular mechanisms of lncRNAs in pancreatic cancer are still unclear. Recent studies have reported that many lncRNAs are dysregulated in pancreatic cancer and closely associated with tumorigenesis, diagnosis and prognosis. In this review, we described the regulation and functional role of lncRNAs and the potential underlying mechanism involved in pancreatic cancer, outlined the roles of lncRNA in pancreatic cancer, and discussed the potential possibility of lncRNAs as therapeutic targets in clinical practice. Moreover, the potential of lncRNAs used as sensitive biomarkers for diagnosis, prognosis and prediction of response to therapy in pancreatic cancer will also be discussed.

The role of imaging in determining prognosis for primary sclerosing cholangitis: A systematic review Dan Segal, Paul Marotta, Mahmoud Mosli, Guangyong Zou, Brian G Feagan, Bandar Al-Judaibi Saudi Journal of Gastroenterology 2019 25(3):152-158 Background/Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression. Materials and Methods: We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). Results: The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression. Conclusion: In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation.

Maladaptive coping, low self-efficacy and disease activity are associated with poorer patient-reported outcomes in inflammatory bowel disease Che-Yung Chao, Carolyne Lemieux, Sophie Restellini, Waqqas Afif, Alain Bitton, Peter L Lakatos, Gary Wild, Talat Bessissow Saudi Journal of Gastroenterology 2019 25(3):159-166 Background/Aims: Patient-reported outcomes (PRO) are key aspects in the management of inflammatory bowel disease (IBD). This study aims to evaluate factors associated with adverse PRO, including modifiable social constructs of maladaptive coping and self-efficacy as well as physician–patient concordance on PRO. Patients and Methods: This cross-sectional study was performed in patients with Crohn's disease (CD) or ulcerative colitis (UC) from September 2015 to March 2016. Validated questionnaires were used to assess quality of life (Short IBD Questionnaire), disability (IBD disability index), productivity (work productivity and activity impairment questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale), coping strategies [Brief Coping Operations Preference Enquiry (Brief COPE)], and self-efficacy (General Self-Efficacy Scale). Independent physician assessment was used to compare concordance with patients. Results: In all, 207 (CD: 144 and UC: 63) patients, with median age of 39 years, were included, with 42.5% males. Significant proportion of patients reported moderate/severe impairment of disability (30.5%), quality of life (29.4%), productivity (52.4%), anxiety (32.9%) and depression (23.3%). Disease activity and maladaptive coping were independently associated with unfavourable PRO, whereas self-efficacy had a positive effect in multivariate analysis. Physicians could accurately identify the magnitude of PRO impairment in standard clinical settings (r = 0.59–0.65, P < 0.001). Conclusion: Disease activity and modifiable psychological constructs are associated with unfavorable PRO in patients with IBD. These factors could assist with identifying high-risk patients, many of whom may benefit from targeted interventions to improve health outcomes.

Cytochrome P450 family members are associated with fast-growing hepatocellular carcinoma and patient survival: An integrated analysis of gene expression profiles Zhao-Zhen Liu, Li-Na Yan, Chun-Nan Dong, Ning Ma, Mei-Na Yuan, Jin Zhou, Ping Gao Saudi Journal of Gastroenterology 2019 25(3):167-175 Background/Aims: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study. Materials and Methods: In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets. Results: From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754–0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716–0.995, P = 0.033). Conclusions: In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence.

Outcome of biliary atresia among Saudi children: A tertiary care center experience Sinan Holdar, Badr Alsaleem, Ali Asery, Abdulrahman Al-Hussaini Saudi Journal of Gastroenterology 2019 25(3):176-180 Background/Aims: Data from Western countries indicate that biliary atresia (BA) is the leading cause of end-stage liver disease in children and the most common indication for liver transplantation (LT) in the pediatric population. There is no data on the epidemiology and outcome of BA in Saudi Arabia. The main objective of our study was to understand the clinical and epidemiological characteristics and outcome of BA in the Saudi population. Patients and Methods: We retrospectively reviewed the database of infantile cholestasis cases that presented to our center from 2008 to 2015 and identified BA cases. Data on clinical, biochemical, imaging, and histopathological characteristics were collected by chart review. The two primary study outcomes were (1) successful Kasai portoenterostomy (KPE) defined as resolution of jaundice (total serum bilirubin <20 μmol/L) and (2) survival with native liver. Results: Over the study period, we evaluated 450 cases of infantile cholestasis. In all, 21 cases (11 males) were diagnosed with BA (4.7%). BA cases were first seen by pediatric gastroenterologists at a median age of 65 days. KPE was performed in 12 cases at a median age of 73 days. Successful KPE was achieved in four cases (33%). Five of the remaining eight cases had LT and three died before LT. Nine of the 21 BA cases were denied KPE and had primary LT at median 8 months of age. The native liver 4-year survival rate was 14.3% and the overall survival rate was 81%. Conclusion: BA is an uncommon cause of infantile cholestasis in Saudi Arabia. Our study provides a snapshot of the epidemiology of BA in Saudi Arabia that is characterized by late referral to pediatric gastroenterologists and poor outcome without LT.

Helicobacter pylori DNA promotes cellular proliferation, migration, and invasion of gastric cancer by activating toll-like receptor 9 Xiang-Rong Qin, Jia Wu, Xin-Yu Yao, Jin Huang, Xiao-Yong Wang Saudi Journal of Gastroenterology 2019 25(3):181-187 Background/Aim: Helicobacter pylori (H. pylori) infection is a well-known risk factor for gastric cancer. Toll-like receptor 9 (TLR9) plays an important role in many cancers and is important for immunity to H. pylori infection. Thus, the present study aimed to evaluate the influence of H. pylori on TLR9 and explore its roles in gastric cancer. Materials and Methods: TLR9 expression in MKN45 cells, which were cocultured with or without H. pylori or H. pylori DNA, was detected using quantitative reverse transcription-polymerase chain reaction and Western blot assays. Then, TLR9 was knocked down through RNA interference technology in MKN45 cells. Cell Counting Kit-8 assay was performed to investigate cell proliferation, and the Transwell system was established to test the migrative and invasive abilities of MKN45 cells. Results: H. pylori infection or H. pylori DNA level was positively correlated with TLR9 upregulation in MKN45 cells. In vitro, H. pylori DNA significantly accelerated cell proliferation and promoted the migration and invasion in MKN45 cells. In contrast, the knockdown of TLR9 significantly suppressed cell proliferation and inhibited the migration and invasion in MKN45 cells. Conclusions: The present results suggest that the H. pylori DNA/TLR9-signaling pathway plays an important role in gastric cancer, which might be a potential therapeutic target.

Recovery of cognitive function after sedation with propofol for outpatient gastrointestinal endoscopy Sanath Allampati, Sijin Wen, Feiyu Liu, Justin T Kupec Saudi Journal of Gastroenterology 2019 25(3):188-193 Background/Aim: Most endoscopies performed in the United States utilize sedation. Anesthesia provides patient comfort and improved procedural quality but adds to the complexity of scheduling routine outpatient procedures. We aimed to assess the return of cognitive function after propofol administration in patients undergoing outpatient endoscopies. Patients and Methods: Cognitive recovery for patients undergoing endoscopy under monitored anesthesia care was evaluated using EncephalApp. Patients were tested before and after procedure and healthy controls were tested twice, 30 min apart. Results were tabulated in on state (on time) and off state (off time) and total time (on time + off time). The time difference between pre- and post-tests, “delta,” was calculated for on, off, and total times. Wilcoxon rank test was used to check the difference in mean delta of all three test times between cases and controls and to check for statistical significance. Results: The difference in mean time between cases and controls was significant for off (P < 0.0001) and total (P = 0.0002) times. No statistically significant difference was noted in mean time for on time (P = 0.013) between cases and controls. Cognitive flexibility, a measure of on time, returned to baseline after procedural sedation even though psychomotor speed, a measure of off time and total time, had not. Conclusion: Cognitive flexibility returns to baseline within 30–45 min after propofol sedation despite delayed return of psychomotor speed and reaction time.

Greater prevalence of comorbidities with increasing age: Cross-sectional analysis of chronic hepatitis B patients in Saudi Arabia Faisal M Sanai, Hamdan Alghamdi, Khalid A Alswat, Mohammed A Babatin, Mona H Ismail, Waleed K Alhamoudi, Abduljaleel M Alalwan, Yaser Dahlan, Abdullah S Alghamdi, Faleh Z Alfaleh, Abdulrahman A Aljumah, Ibrahim H Altraif, Khalid Albeladi, Faisal Batwa, Waleed Alshumrani, Drifa Belhadi, Victor Genestier, Ayman A Abdo Saudi Journal of Gastroenterology 2019 25(3):194-200 Background/Aims: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. Patients and Methods: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). Results: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1–12%) and cirrhosis (range 5–23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1–2% in 2010/2012). Conclusions: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.

Bone mineral density loss in patients with cirrhosis Mahmood Dhahir Al-Mendalawi Saudi Journal of Gastroenterology 2019 25(3):201-201

Fertility Science and Research

Changing concepts in IVF: Are we prepared? Kuldeep Jain Fertility Science and Research 2018 5(2):37-40

Endometritis in infertility Pinkee Saxena, Surveen G Sindhu Fertility Science and Research 2018 5(2):41-47 Chronic endometritis is an asymptomatic condition. It results from persistent inflammation of the endometrial lining caused by the presence of microorganisms in the uterine cavity. It is often associated with infertility and poor reproductive outcome. The pathogenesis of chronic endometritis and its association with infertility has been reviewed. Diagnostic modalities and treatment for chronic endometritis are also discussed.

The impact of acupuncture on IVF success rates: A randomised controlled trial K. Gillerman, A. Kulkarni, A. Shah, A. Gudi, Roy Homburg Fertility Science and Research 2018 5(2):48-54 Background: Clinical trials to assess the benefits of acupuncture on in vitro fertilisation (IVF) treatment have differed in study design, protocol, outcome measures and commercial bias. This heterogeneity has precluded any firm conclusion regarding the efficacy, or otherwise, of acupuncture in this field. To address this, 15 international acupuncturists with experience in treating women during IVF participated in Delphi questionnaires and reached a consensus protocol to be used in future research. We were among the first to adopt this newly agreed standard protocol. The aim of this study was to address whether the agreed acupuncture consensus protocol is beneficial for IVF outcomes and may be offered to women undergoing IVF. Methods: An randomised controlled trial, in which 157 women were randomised to receive either acupuncture treatment three times in the treatment cycle in addition to our standard IVF protocol (n = 79) or no acupuncture treatment (n = 78) in their first or second IVF cycle. They were between 23 and 43 years with body mass index below 30. The study group (n = 79) received acupuncture based on the Delphi consensus protocol, between days 6 and 8 of ovarian stimulation, and twice on the day of embryo transfer, before and after transfer. The IVF practitioner was blinded to the randomisation. The primary end point was live birth. Results: Fifteen out of 79 women in the intervention group withdrew from the study compared to 9/78 women from the control group (P < 0.001). A per-protocol analysis revealed that the rate of live births (27/64, 42% vs. 11/69, 15.94%, P = 0.001) and positive pregnancy tests (34/64, 53% vs. 19/69, 27.53%, P = 0.013) were significantly higher in the acupuncture group compared with the control group. Conclusion: The results of this study imply that acupuncture may be offered as a possible method of improving IVF outcome. This study followed a widely approved consensus protocol hoping to settle disagreement in the literature and resolve previous disparity. Trial Registration: ClinicalTrials NCT02683967.

Effect of the endometriomas on ovarian stimulation and pregnancy rate on assisted reproductive outcomes Dipanshu Sur, Ratnabali Chakravorty, Amitoj Athwal, Aamir Javed Fertility Science and Research 2018 5(2):55-59 Endometriosis is a disease known to be detrimental to fertility. Women with endometriosis, and the presence of endometrioma, may require assisted reproductive technologies to achieve a pregnancy. Aim: Our aim was to evaluate the effect of endometriosis and the presence of an endometrioma on outcomes of conventional in vitro fertilization/intra-cytoplasmic sperm injection (ICSI). Materials and Methods: The study group consisted of 45 infertile women with either unilateral or bilateral ovarian endometrial cysts of less than 3 cm. The control group consisting of 50 patients with mild male factor infertility was candidate for ICSI treatment during the same time period as the study groups. Both groups were compared for number of oocytes retrieved, grades of oocytes, as well as embryo quantity and quality. Results: Our findings showed similar follicle numbers, good embryo grades (I or II) and pregnancy rates in the compared groups. However, patients with endometriosis had higher gonadotropin consumption than the control group. The mean number of retrieved oocytes in patients with endometriosis was significantly lower than control group (P < 0.0001). The numbers of metaphase II (MII) oocytes were significantly lower in patients with endometriosis as compared to the control group 6.11 ± 2.92 vs. 9.32 ± 4.71, respectively (P = 0.0002). In patients with unilateral endometriosis, there were significant differences in terms of fertilization rate, retrieved oocyte and MII oocyte between the normal and involved ovaries; P < 0.5. Conclusion: The endometriomas group had a significantly poorer ovarian response and required significantly more ampoules of follicle-stimulating hormone per cycle. They showed poor ovarian response with lower total numbers of retrieved oocytes and lower MII oocytes during the stimulation phase; however, it does not affect the quality of embryos and pregnancy rate per patient.

Assessing the possible risk factors of male infertility Trilok Shrivastava, Uma S Pokhrel, Sumina Shrestha, Sanjeev Shrestha Fertility Science and Research 2018 5(2):60-64 Background: Male infertility encompasses up to 50% of all infertility cases and can be due to a variety of causes. Besides cytogenetic abnormalities, hormonal and environmental factors such as trauma, heat, toxins, radiation and nutritional deficiency have been shown to affect spermatogenesis. This study aims to look for the possible risk factors that impair the normal sperm production, which is reflected in semen analysis. Materials and Methods: A total of 601 men underwent semen analysis at Infertility Centre in this prospective case–control study. After undergoing semen analysis, those with azoospermia (AZ), oligozoospermia (OL) and asthenozoospermia (AS) were selected as cases of the study, whereas those with normal semen analysis results were selected as controls. All participants were interviewed with a standardised questionnaire to assess for the known & possible risk factors of infertility & data was analysed. Results: Mean & standard deviation (SD) age of the participants was 33.38 ± 5.63 years. History of varicocele was found to be significantly associated with AZ/OL [adjusted odds ratio (ORadj) 5.4] and AS (ORadj 6.9). Similarly, men with a history of mumps orchitis had a significant association with both AS (ORadj 2.13) and OL/AZ (ORadj 2.62). Men who chewed tobacco had about twice more chances of having OL/AZ. Activities related to scrotal heat exposure except hot water bath were not associated with sperm quality [AS (ORadj 0.68) and OL/AZ (ORadj 0.59)]. Motorcycle riders were found to have decreased association with low semen quality AS (ORadj 0.53) and OL/AZ (ORadj 0.50). Conclusion: Varicocele, mumps orchitis and tobacco chewing are significant risk factors that have shown to decrease semen quality and can contribute to male infertility.

A rare case of ruptured twin tubal ectopic pregnancy Pinkee Saxena, Poonam Laul, Gunjan Chaudhary, Vijay K Kadam Fertility Science and Research 2018 5(2):65-67 Twin tubal ectopic pregnancies are rare forms of ectopic pregnancies, with an incidence of one in 200 ectopic pregnancies. We present a rare case of ruptured ectopic pregnancy which occurred due to twin tubal pregnancy. This was a spontaneous pregnancy with no risk factor for ectopic pregnancy.

Pregnancy after DHEA-S for low ovarian reserve due to laparoscopic ovarian drilling Paapa Dasari, Ashraf M Ali Fertility Science and Research 2018 5(2):68-71 A 32-year-old married for three years, who had taken treatment for primary infertility, approached for assisted reproductive techniques (ART) after the failure of 10 cycles of ovulation induction with clomiphene citrate (CC) and laparoscopic ovarian drilling (LOD) two years ago. She was evaluated and found to have anti-Mullerian hormone (AMH) of 0.63 ng/ml and antral follicle count (AFC) of four and was treated with dehydroepiandrosterone sulphate (DHEA-S) for three months. Her AMH increased to 1.2 ng/ml and AFC to seven and she underwent three cycles of ovulation induction and intrauterine insemination (IUI) which was unsuccessful. She conceived naturally after the fourth cycle of ovulation induction with gonadotropins without cycle monitoring. Her Pregnancy was supported with progesterone until 36 weeks, and she underwent elective lower segment Caesarean section (LSCS) for mid-pelvic contraction at 38 weeks of pregnancy. The Caesarean section inspection of the ovaries showed bilateral charring and a few tubo-tubal adhesions. Her postoperative period was normal and mother and baby were discharged on the fifth postnatal day.

Pharmacology

Pattern of pharmacological research from the last six decades Rupa Joshi, Saniya Mahendiratta, Ajay Prakash, Bikash Medhi Indian Journal of Pharmacology 2019 51(2):85-87

Wound healing effects of topical Vitamin K: A randomized controlled trial Nader Pazyar, Gholamreza Houshmand, Reza Yaghoobi, Ali Asghar Hemmati, Zahra Zeineli, Behnam Ghorbanzadeh Indian Journal of Pharmacology 2019 51(2):88-92 BACKGROUND: The incidence of acute and chronic wounds has rapidly increased which treatment remains as health problem. Previously, we reported the healing effect of Vitamin K in experimental animal models. The aim of this study was to investigate the effects of topical Vitamin K on skin wound healing process in patients. MATERIALS AND METHODS: Sixty-three patients with indication for high-frequency electrocautery were enrolled in this randomized controlled trial. The patients were divided randomly into three groups. All the patients underwent high-frequency electrocautery treatment. Then, the patients in the A group received 1% Vitamin K cream, the patients in the B group received 1% phenytoin cream. Furthermore, the patients in the control group received Eucerin. The wound status (width and the time of recovery) and complications in the three groups were evaluated 2 weeks after procedure by a dermatologist. RESULTS: The effects produced by the topical Vitamin K showed a significant (P < 0.05) healing when compared with Eucerin group in parameters such as wound contraction and time to full recovery. Moreover, the healing time did not differ between phenytoin and Vitamin K groups (P = 0.16). CONCLUSION: A randomized, controlled trial suggests that topical application of Vitamin K significantly reduces healing time in patients.

Change in antiepileptic drug prescription patterns for pregnant women with epilepsy over the years: Impact on pregnancy and fetal outcomes Ramandeep Bansal, Vanita Suri, Seema Chopra, Neelam Aggarwal, Pooja Sikka, Subhas Chandra Saha, Parampreet Singh Kharbanda, Praveen Kumar Indian Journal of Pharmacology 2019 51(2):93-97 AIMS AND OBJECTIVES: The objectives of the study were: (1) to determine if there is a change in pattern of antiepileptic drug (AED) prescription during pregnancy in women with epilepsy (WWE) attending a tertiary care institute in North India and (2) to determine if change in AED prescription pattern has resulted in improved fetal and maternal outcomes in WWE. PATIENTS AND METHODS: The current study was a retrospective analysis of records of WWE attending a medical and surgical disorder clinic of obstetrics and gynecology department of a tertiary care teaching hospital in North India. We retrospectively collected data of all the patients during the 5-year period from 2011 to 2015 (Group A) (n = 177) and compared it with our previously published data during the years 1987–1994 (Group B) (n = 219). RESULTS: There was significantly higher use of (i) levetiracetam (LEV) in Group A compared to Group B when women on monotherapy were compared (P<0.0001) and (ii) LEV (P<0.0001), clobazam (P<0.0001) and lamotrigine (P=0.0004) in Group A compared to Group B when women on polytherapy were compared. A significantly higher (P=0.02) number of women were using more than two antiepileptic drugs simultaneously in Group A compared to Group B. There was a significantly higher incidence (P = 0.001) of small for gestational age babies in Group A. CONCLUSION: Although there is an increase in the use of newer AEDs in WWE during pregnancy in North Indian population, it has not resulted in improved maternal and fetal outcomes. (2) to determine if change in AED prescription pattern has resulted in improved fetal and maternal outcomes in WWE.

Antidepressant-like effect of a standardized hydroethanolic extract of Asparagus adscendens in mice Priyanka Pahwa, Rajesh Kumar Goel Indian Journal of Pharmacology 2019 51(2):98-108 OBJECTIVE: Asparagus adscendens Roxb. (Liliaceae), a traditional herbal medicine, has been used as an aphrodisiac and brain tonic in Asian countries. The aim of the present study is to investigate the antidepressant-like effect of standardized hydroethanolic extract of A. adscendens root and its possible mechanisms. MATERIALS AND METHODS: Mice administered with vehicle, imipramine (15 mg/kg/day; i.p.), and A. adscendens extract (AAE) (25, 50, and 100 mg/kg/day; i.p.) for 14 days were subjected to behavioral tests including forced swimming test (FST), tail suspension test (TST), and open-field test (OFT) on the 14th day. In order to explore the underlying mechanism behind an antidepressant effect of AAE, the brain monoamine levels, oxidative stress parameters, and serum corticosterone levels were monitored. RESULTS: Our results indicated that pretreatment of AAE (25, 50, and 100 mg/kg) for 14 days statistically significantly (P < 0.01) demonstrated antidepressant-like effect as evidenced by reduced immobility time in both FST (105, 78.6, and 53.6 s) and TST (97.6, 73.5, and 54.67 s), with no significant change in spontaneous locomotor activities as observed in OFT. Further, the behavioral improvement was supported by the statistically significantly (P < 0.05) enhanced levels of monoamines and reduced corticosterone level along with amelioration of oxidative stress in AAE-treated animals as compared to vehicle control group. Conclusion: Our findings clearly demonstrated the antidepressant-like effect of AAE, which might have been mediated through the modulation of monoaminergic system and by regulating hypothalamic–pituitary–adrenal axis with amelioration of oxidative stress.

Curricular adequacy on basics of clinical trials Sonu Gupta, Ravinder Nath Bansal Indian Journal of Pharmacology 2019 51(2):109-115 INTRODUCTION: Clinical trials are integral to innovation in the treatment modalities and are conducted to assess the safety and efficacy of novel drugs. Clinical trials of modern era have evolved through stern consequences and tragedies in the past. This study was designed to know knowledge on ethics, adverse drug reactions (ADRs), and tragedies in clinical trials among interns and postgraduates (PGs). METHODOLOGY: A cross-sectional study was carried out on graduates undergoing internship (interns) and PG residents of a medical college and a dental college from Punjab. This descriptive cross-sectional study was conducted on 151 professionals of medical college and 100 professionals of dental colleges in Punjab with the help of a prevalidated questionnaire. The data were then analyzed using descriptive statistics. RESULTS: There was no significant difference between dental and medical doctors regarding ethics and ADRs, but a significant difference was observed among interns and PG residents, with interns having higher awareness regarding ethics and ADRs. There was no significant difference (P = 0.941) in knowledge among dental and medical doctors as well as among interns and PG residents, with P = 0.264 about tragedies in clinical trials. CONCLUSION: From the study, it can be concluded that interns and PGs do not get enough exposure to basics in clinic research such as research ethics, ADRs, and tragedies in clinical trials. It is suggested that there is a requirement for suitable modifications in the teaching curriculum at undergraduate level and regular training must be provided to professionals.

Efficacy of oral terbinafine versus itraconazole in treatment of dermatophytic infection of skin – A prospective, randomized comparative study Anuradha Bhatia, Bimal Kanish, Dinesh Kumar Badyal, Prajakta Kate, Swati Choudhary Indian Journal of Pharmacology 2019 51(2):116-119 OBJECTIVES: Dermatophytic infections are the common fungal infections aggravated by hot and humid climate. Terbinafine and itraconazole are commonly used oral antifungal agents for the same. However, resistance to these drugs is being seen increasingly when used in the conventional doses and duration. Therefore, this study was designed to compare the efficacy of terbinafine and itraconazole in increased dosages and duration in the treatment of tinea corporis and tinea cruris. MATERIALS AND METHODS: In this randomized comparative study, patients of tinea cruris and tinea corporis were randomly divided into two groups of 160 each and were given oral terbinafine (Group I) and oral itraconazole (Group II) for 4 weeks. The scores and percentage change in scores of pruritus, scaling, and erythema were evaluated at 2 and 4 weeks. RESULTS: At the end of week 4, mycological cure was seen in 91.8% after 4 weeks in the itraconazole group as compared to 74.3% of patients in the terbinafine group. There was a significant improvement in percentage change in pruritus, scaling, and erythema in both the groups from 0 to 4 weeks. On comparing groups, the percentage change was significantly different in scaling from 0 to 2 weeks (5.4 vs. −4.8) and 2–4 weeks (16.7 vs. 29.6) between Group I and Group II, respectively. Clinical global improvement was better with itraconazole. Mild adverse effects such as gastrointestinal upset, headache, and taste disturbances were observed which were comparable in both the groups. CONCLUSIONS: Itraconazole and terbinafine seem to be equally effective and safe in the treatment of tinea cruris and tinea corporis.

Phenytoin-induced bradycardia and hypotension Swetha Reba Mathews, Dinesh Kumar Badyal, Renji Mathew Indian Journal of Pharmacology 2019 51(2):120-122 Phenytoin is an anticonvulsant which is also a Class IB antiarrhythmic. Its common adverse drug reactions (ADRs) include gastrointestinal symptoms, psychiatric disorders, gingival hyperplasia, and rash. Bradycardia and hypotension following intravenous (IV) phenytoin are rare ADRs. We report the case of a 62-year-old female with subarachnoid hemorrhage and right bundle branch block, who developed sinus bradycardia and hypotension on administration of IV phenytoin. This case report serves as a note for caution on patient selection for the administration of phenytoin and highlights the need for specific guidelines on the same.

Levofloxacin-induced tactile hallucination and acute anxiety reaction B Maharani, A Lourdu Jafrin, K Vyshnavi Bai, G Sivagnanam Indian Journal of Pharmacology 2019 51(2):123-125 Fluoroquinolones are the commonly used antimicrobials in the treatment of urinary tract infection, bacterial diarrhea, and infections of soft tissue, bone, and joints. They may cause adverse effects ranging from gastrointestinal disturbances, headache, insomnia, and cutaneous reactions. Their rare adverse effects include phototoxicity, cardiotoxicity, arthropathy, and tendinitis. Among the fluoroquinolones, levofloxacin has more propensity to cause the central nervous system adverse effects such as headache, tremor, insomnia, dizziness, convulsions, psychosis, auditory, and visual hallucinations. A case of acute sinusitis in a young male treated with levofloxacin presented with tactile hallucination and acute anxiety reaction is reported for its rarity of occurrence. According to the Naranjo causality scale, the association of tactile hallucination and acute anxiety is a probable adverse drug reaction due to levofloxacin.

Time to take stock of Indian regulatory guidelines regarding drug use in pregnancy and lactation Aashima Arora, Amol Patil Indian Journal of Pharmacology 2019 51(2):126-127